Abstract LB-210: A multiplexed serum biomarker immunoassay panel discriminates clinical lung cancer patients from cancer-free high-risk subjects in a CT-screened cohort

Abstract

Abstract Clinical decision making in the setting of CT screening could benefit from accessible biomarkers that help predict the level of lung cancer risk in high-risk subjects with indeterminate pulmonary nodules commonly found by screening. The specificity and sensitivity needed to improve interpretation of CT images in the setting of a suspicious pulmonary nodule would be less stringent than those needed for lung cancer screening in the general population. As a first step in identifying and characterizing serum protein biomarkers to more accurately identify individuals with lung cancer in populations of high-risk tobacco-exposed individuals, we measured 70 cancer-related proteins by Luminex xMAP® multiplexed immunoassays in a training set of sera from 56 patients with biopsy-proven primary lung cancer diagnosed in a clinical setting and sera from 56 age-, sex- and smoking-matched CT-screened controls. These controls are drawn from a cohort of participants in the Pittsburgh Lung Screening Study (PLuSS) who have undergone CT screening and are known to be cancer-free after a minimum of 3 years follow-up. We found a profile of 8 biomarkers - PRL, TTR, THSP, SELE, CCL5, MIF, and SERPINE1 and ERBB2 - that distinguished lung cancer from controls in the training set with a sensitivity (SN) of 92.9% and specificity (SP) of 87.5%. The balanced accuracy (average of SN and SP) from 20-fold internal cross-validation of the training set was 82.5% ± 4.8%. We then applied this 8 biomarker model to an independent test set of 10 additional clinically detected lung cancer cases and 83 randomly selected PLuSS participants who were known to be cancer-free. These PLuSS controls in the test set included subjects with and without CT-detected pulmonary nodules and a range of airflow obstruction and radiographic emphysema. The biomarker model classified these test set cases and controls with a balanced accuracy of 83.6% (90.0% SN and 77.1% SP). Importantly, the misclassified PLuSS controls in the test set displayed no significant association with airway function variables or level of suspicion of pulmonary nodule. Taken together, these data suggest that the 8 biomarker panel classified lung cancer independently of pulmonary function abnormalities and the presence of non-cancerous pulmonary nodules, and thus may provide clinical utility in ruling out lung cancer in tobacco-exposed individuals screened by CT imaging. [Supported by NCI SPORE in Lung Cancer P50 CA090440 (JMS) and NCI Early Detection Research Network Biomarker Discovery Laboratory U01 CA084968 (WLB)]. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr LB-210.